1. Technical Field of the Invention
The present invention relates to pharmaceutical compositions based on a compound of the avermectin family, in the form of a cream-gel comprising, formulated into a physiologically acceptable medium, an oily phase dispersed in an aqueous phase by means of a non-surfactant polymeric emulsifier, said oily phase comprising oils having a melting point below 30° C. and being free or devoid of solid fats having a melting point above 30° C.
This invention also relates to a process for preparing such pharmaceutical compositions and to their utilization in the production of pharmaceutical preparations suited for the treatment of dermatological conditions, disorders or afflictions, in particular of rosacea.
2. Description of Background and/or Related and/or Prior Art
Ivermectin is a mixture of two compounds belonging to the avermectin class, 5-O-demethyl-22,23-dihydroavermectin A1a and 5-O-demethyl-22,23-dihydroavermectin A1b. They are also known as 22,23-dihydroavermectin B1a and 22,23-dihydroavermectin B1b. Ivermectin contains at least 80% of 22,23-dihydroavermectin B1a and less than 20% of 22,23-dihydroavermectin B1b. This active agent is part of the avermectin class, a group of macrocyclic lactones produced by the bacterium Streptomyces avermitilis (Reynolds J E F (Ed) (1993) Marindale. The extra pharmacopoeia. 29th Edition. Pharmaceutical Press, London). The avermectins include, in particular, ivermectin, invermectin, avermectin, abamectin, doramectin, eprinomectin and selamectin.
Ivermectin is more particularly an anthelmintic. It has already been described in humans in the treatment of river blindness caused by Onchocerca volvulus, of gastrointestine strongyloidosis (anguillulosis) (product Stromectol®), and of human scabies (Meinking T L et al., N. Engl. J. Med., 1995 Jul. 6; 333(1):26-30 The treatment of scabies with ivermectin) and also in the treatment of microfilaremia diagnosed or suspected in individuals suffering from lymphatic filariasis due to Wuchereria bancrofti. 
U.S. Pat. No. 6,133,310 discloses administering ivermectin topically in the form of a lotion consisting of a mixture of ivermectin and water, and also mentions the possibility of a cream consisting, for its part, of a mixture of ivermectin and an excipient such as propylene glycol or sodium lauryl sulfate, but describes no pharmaceutical composition that is industrially acceptable, i.e., having good cosmeticity and a sufficiently long shelf-life (minimum of 2 years).
Dermatological conditions are often associated with increased sensitivity of the skin, particularly in the case of rosacea, which is an inflammatory dermatosis that affects mainly the central part of the face and is characterized, inter alia, by reddening of the face, hot flashes, and facial erythema. This type of pathology requires particularly the use of pharmaceutical formulations that are easy to spread and impart to the user a pleasant feeling of well-being.
Need, therefore, continues to exist for topical pharmaceutical compositions containing at least one compound of the avermectin family, and more particularly ivermectin, which are completely suitable for the pathology and specifically for sensitive skin, which is industrially acceptable, i.e., the formulation of which is physically stable (without phase separation) and chemically stable (without modification of the stability of the active agent), and which optimizes the penetration of ivermectin into the skin.